The Compound DOPAL was synthesized from the reaction done by Robins et al. A solution of adrenaline (227.74 mg, 1.243mmol) in 85% phosphoric acid (6 mL) was heated in a 12mL vial via a Glycerol bath. The vial was placed into the bath at 100C and then heated to 120C for 15 min then removed from heat and allowed to cool for 30 seconds. The solution was added to distilled water (36 mL) and allowed to sit for 1.5 hours. It was then saturated with NaCl. The solution was decanted off of the excess sodium chloride into a separatory funnel. The aldehyde was then extracted with ethyl ether (15 mL, 15 mL, 10mL), which were combined and dried over MgSO4. After filtration the solution was evaporated to yield crude DOPAL (15.6 mg, 1.22 mmol, 6.85 %yield). See Exp 016.
Ugi Reaction Procedure
Prepared solutions of piperonal(150.3 mg, 1 mmol, 2 mL CDCl3, 0.5 M) and aniline(91 uL, 1 mmol, 2 mL CDCl3, 0.5 M). Mixed aldehyde and amine solutions together in a 13 mL vial in the presence of 97(approximately 98mg) 3A molecular sieves. Solution turned pale yellow. Took three HMRs over 40 hour period. Added 415 mg of MgSO4 to imine solution to remove water generated from reaction. Shook well and let sit for several minutes. Filtered solution into new 13 mL vial. Prepared a solution of Boc-Gly-OH(188.0 mg, 1.07 mmol, 2 mL CDCl3, 0.536 M) and tert-butylisocyanide(113 uL, 1 mmol, 2 mL CDCl3, 0.5 M) in 2 mL volumetric flasks. Added the two solutions in a 5 mL volumetric flask shook well and then added to imine solution. Solution turned deep yellow to orange in color. Took one HMR. See Exp084
Imine Reversal Reaction
Made 2M solutions of piperonal (240mg, 1.6mmol), and Boc-Gly-OH (280mg, 1.6mmol), while 2-morpholinoethyl isocyanide (220uL, 1.6mmol) was made at a 1.56M concentration and tert-butylamine (168uL, 1.6mmol), was made at a 1.65M concentration. All solutions were made with 800uL of MeOH-d4. A volume of 400uL of each starting material was taken and diluted with another 400uL of MeOH-d4 making each 1M. HMRs were taken of each starting material. The remaining 400uL 2M of piperonal and tert-butylamine were added together giving each a concentration of 1M to each component. HMRs were taken over a period 94mins. The remaining 400uL 2M of Boc-Gly-OH was added to the solution of aldehyde and amine giving a concentration of 0.75M for each component. HMRs were taken over the next 20mins. Because the volume of solution was becoming too much for the NMR tube, the solution in the NMR tube was transfered to a 5 dram vial and the remaining 400uL of isocyanide was added to the solution and 800uL was pipetted into the same NMR tube. HMRs were taken over 77 mins. All HMRs were done on a Varian 300MHz NMR. See Exp048
Experimental
DOPAL Procedure
The Compound DOPAL was synthesized from the reaction done by Robins et al. A solution of adrenaline (227.74 mg, 1.243mmol) in 85% phosphoric acid (6 mL) was heated in a 12mL vial via a Glycerol bath. The vial was placed into the bath at 100C and then heated to 120C for 15 min then removed from heat and allowed to cool for 30 seconds. The solution was added to distilled water (36 mL) and allowed to sit for 1.5 hours. It was then saturated with NaCl. The solution was decanted off of the excess sodium chloride into a separatory funnel. The aldehyde was then extracted with ethyl ether (15 mL, 15 mL, 10mL), which were combined and dried over MgSO4. After filtration the solution was evaporated to yield crude DOPAL (15.6 mg, 1.22 mmol, 6.85 %yield). See Exp 016.Ugi Reaction Procedure
Prepared solutions of piperonal(150.3 mg, 1 mmol, 2 mL CDCl3, 0.5 M) and aniline(91 uL, 1 mmol, 2 mL CDCl3, 0.5 M). Mixed aldehyde and amine solutions together in a 13 mL vial in the presence of 97(approximately 98mg) 3A molecular sieves. Solution turned pale yellow. Took three HMRs over 40 hour period. Added 415 mg of MgSO4 to imine solution to remove water generated from reaction. Shook well and let sit for several minutes. Filtered solution into new 13 mL vial. Prepared a solution of Boc-Gly-OH(188.0 mg, 1.07 mmol, 2 mL CDCl3, 0.536 M) and tert-butylisocyanide(113 uL, 1 mmol, 2 mL CDCl3, 0.5 M) in 2 mL volumetric flasks. Added the two solutions in a 5 mL volumetric flask shook well and then added to imine solution. Solution turned deep yellow to orange in color. Took one HMR. See Exp084Imine Reversal Reaction
Made 2M solutions of piperonal (240mg, 1.6mmol), and Boc-Gly-OH (280mg, 1.6mmol), while 2-morpholinoethyl isocyanide (220uL, 1.6mmol) was made at a 1.56M concentration and tert-butylamine (168uL, 1.6mmol), was made at a 1.65M concentration. All solutions were made with 800uL of MeOH-d4. A volume of 400uL of each starting material was taken and diluted with another 400uL of MeOH-d4 making each 1M. HMRs were taken of each starting material. The remaining 400uL 2M of piperonal and tert-butylamine were added together giving each a concentration of 1M to each component. HMRs were taken over a period 94mins. The remaining 400uL 2M of Boc-Gly-OH was added to the solution of aldehyde and amine giving a concentration of 0.75M for each component. HMRs were taken over the next 20mins. Because the volume of solution was becoming too much for the NMR tube, the solution in the NMR tube was transfered to a 5 dram vial and the remaining 400uL of isocyanide was added to the solution and 800uL was pipetted into the same NMR tube. HMRs were taken over 77 mins. All HMRs were done on a Varian 300MHz NMR. See Exp048Back to my page
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Results